ABSTRACT: OBJECTIVES: To determine which easily available clinical factors are associated with mortality in patients with stable COPD and if health-related quality of life (HRQoL) provides additional information. DESIGN: Five-year prospective cohort study. SETTING: Five outpatient clinics of a teaching hospital. PARTICIPANTS: Six hundred stable COPD patients recruited consecutively. MEASUREMENTS: The variables were age, FEV(1%), dyspnea, previous hospital admissions and emergency department visits for COPD, pack-years of smoking, comorbidities, body mass index, and HRQoL measured by Saint George's Respiratory Questionnaire (SGRQ), Chronic Respiratory Questionnaire (CRQ), and Short-Form 36 (SF-36). Logistic and Cox regression models were used to assess the influence of these variables on mortality and survival. RESULTS: FEV(1%)(OR: 0.62, 95% CI 0.5 to 0.75), dyspnea (OR 1.92, 95% CI 1.2 to 3), age (OR 2.41, 95% CI 1.6 to 3.6), previous hospitalization due to COPD exacerbations (OR 1.53, 1.2 to 2) and lifetime pack-years (OR 1.15, 95% CI 1.1 to 1.2) were independently related to respiratory mortality. Similarly, these factors were independently related to all-cause mortality with dyspnea having the strongest association (OR 1.54, 95% CI 1.1 to 2.2). HRQoL was an independent predictor of respiratory and all-cause mortality only when dyspnea was excluded from the models, except scores on the SGRQ were associated with all-cause mortality with dyspnea in the model. CONCLUSIONS: Among patients with stable COPD, FEV(1%) was the main predictor of respiratory mortality and dyspnea of all-cause mortality. In general, HRQoL was not related to mortality when dyspnea was taken into account, and CRQ and SGRQ behaved in similar ways regarding mortality.